The goal of this project is to discover the molecular basis of neurochemical transduction mechanisms, using the pineal gland as a model. This program has yielded new information on how Alpha 1-adrenoceptors participate with Beta 1-adrenoceptors in the synergistic regulation of cAMP and cGMP. Alpha 1-Adrenoceptors appear to open a ligand dependent calcium channel, which leads to a 5-fold increase in the apparent intracellular concentration of calcium. In addition Alpha 1-adrenoceptors alter aphospholipid metabolism, by stimulating the activity of both phospholipase A2 and phospholipase C. The combined effects of the increase in calcium and phospholipase C activity potentiates the Beta-adrenergic stimulation of adenylate cyclase; the combined effects of the increase in calcium and of phospholipase A lead to an increase in the Beta-adrenergic stimulation of cGMP. Advances have been made in the purification of pineal N-acetyltransferase and hydroxyindole-O-methyltransferase, in the preparations of antisera against hydroxyindole-O-methyltransferase, preparation of bovine pineal cDNA libraries, cloning the S-antigen from a bovine retina cDNA library. Pineal processes have been described in a species of hamster and preliminary evidence of such processes in the monkey have been obtained.